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1.
Am J Transplant ; 23(9): 1388-1400, 2023 09.
Article in English | MEDLINE | ID: mdl-37257653

ABSTRACT

Technological advances in the field of histocompatibility have allowed us to define anti-human leukocyte antigen (HLA) antibody specificity at the allelic level. However, how allele-specific antibodies affect organ allocation is poorly studied. We examined allelic specificities of class I HLA antibodies in 6726 consecutive serum samples from 2953 transplant candidates and evaluated their impact on the corresponding crossmatch and organ allocation. Out of 17 class I HLA antigens represented by >1 allele in the LABScreen single antigen bead assay, 12 had potential allele-specific reactivity. Taking advantage of our unbiased cohort of deceased donor-candidate testing (123,135 complement-dependent cytotoxicity crossmatches between 2014 and 2017), we estimated that the presence of allele-specific antibody detected using a single antigen bead assay (median fluorescence intensity, >3000) against only the rare allele was a poor predictor of a positive complement-dependent cytotoxicity crossmatch, with a positive predictive value of 0% to 7%, compared with 52.5% in allele-concordant class I HLA antibodies against A or B locus antigens. Further, we confirmed allele-specific reactivity using flow crossmatch in 3 scenarios: A11:01/A11:02, A68:01/A68:02, and B44:02/B44:03. Our results suggest that allele-specific antibodies may unnecessarily exclude transplant candidates (up to 10%) from organ offers by overcalling unacceptable antigens; incorporation of selective reactivity pattern in allocation may promote precision matching and more equitable allocation.


Subject(s)
Histocompatibility Antigens Class I , Isoantibodies , Humans , Alleles , Histocompatibility Testing/methods , Histocompatibility Antigens Class I/genetics , HLA Antigens/genetics , Antigens
2.
Saudi J Kidney Dis Transpl ; 32(1): 183-190, 2021.
Article in English | MEDLINE | ID: mdl-34145129

ABSTRACT

Incidence and prevalence of end-stage kidney disease (ESKD) population on renal replacement therapy (RRT) for some of the nations are well published. Oman's publication on this aspect is limited and therefore, this study was conducted. This study analyzed the data obtained from the RRT register in Oman. The main measurements and aim are to identify the incidence and prevalence of Oman's treated RRT population (1983-2018) with a major focus on the hemodialysis (HD) cohort. The year 1983 is the year when renal care was started in Oman. The total number of patients registered on Oman's RRT register of the central renal dialysis center from 1983 to 2010 was 3524, distributed among the following treatment cohorts; HD, 2328 patients (66%); kidney transplant, 1,144 patients (32.5%); peritoneal dialysis, 52 patients (1.5%). However, the treated patients alive on HD by end of 2018 were 2023. The dialysis sub-population increased from 35 patients in 1983 to 2023 patients in 2018. The recorded incidence registered in 1983 was 34 patients, in 1986 was 33, in 2013 was 168, in 2015 was 230, and in 2018 was 350 RRT treated patients per million population of Oman. There is a progressive rise of the incidence and prevalence of Oman's RRT population. This rise is similar to many nations, especially developing countries that are being faced with the rising trend of noncommunicable diseases (NCD). The health system and other stakeholders ought to take various stringent policies to ameliorate the progressive increase of NCD and hence, reduce the burden of chronic kidney disease and ESKD.


Subject(s)
Kidney Failure, Chronic/epidemiology , Kidney Failure, Chronic/therapy , Renal Dialysis , Cohort Studies , Female , Humans , Incidence , Male , Nephrology , Oman/epidemiology , Prevalence , Time Factors
3.
Oman Med J ; 33(1): 7-14, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29467993

ABSTRACT

OBJECTIVES: This study sought to report 22 years experience in pediatric kidney transplantation in Oman. METHODS: Electronic charts of all Omani children below 13 years of age who received a kidney transplant from January 1994 to December 2015 were reviewed. Data collected included patient demographics, etiology of end-stage kidney disease, modality and duration of dialysis, donor type, complication of kidney transplantation (including surgical complications, infections, graft rejection) graft and patient survival, and duration of follow-up. RESULTS: During the study period transplantation from 27 living related donors (LRDs), 42 living unrelated donors (LURDs), also referred to as commercial transplant, and one deceased donor were performed. The median age at transplantation was nine years for both groups. The most common primary diagnosis was congenital anomalies of the kidney and urinary tract in 32.8% of patients followed by familial nephrotic syndrome in 20.0% and polycystic kidney disease in 18.5%. Almost half the patients were on hemodialysis before transplantation, 35.7% were on peritoneal dialysis, and 14.2% received preemptive renal transplantation. Children who received LURD kidneys had high surgical complications (42.8%) compared to the LRDs group (17.8%). Five patients from LURDs group had early graft nephrectomy and four patients developed non-graft function or delayed graft function. In addition, patients in the LURDs group had a higher incidence of hypertension and acute rejection. Graft and patient survival were both better in the LRDs than the LURDs group. CONCLUSIONS: Although our pediatric kidney transplant program is a young program it has had successful patient outcomes comparable to international programs. Our study provides evidence that in addition to legal and ethical issues with commercial transplant, it also carries significantly higher morbidity and reduced graft and patient survival.

4.
Pediatr Nephrol ; 33(3): 473-483, 2018 03.
Article in English | MEDLINE | ID: mdl-29058154

ABSTRACT

BACKGROUND: Familial steroid-sensitive nephrotic syndrome (SSNS) is a rare condition. The disease pathophysiology remains elusive. However, bi-allelic mutations in the EMP2 gene were identified, and specific variations in HLA-DQA1 were linked to a high risk of developing the disease. METHODS: Clinical data were analyzed in 59 SSNS families. EMP2 gene was sequenced in families with a potential autosomal recessive (AR) inheritance. Exome sequencing was performed in a subset of 13 families with potential AR inheritance. Two variations in HLA-DQA1 were genotyped in the whole cohort. RESULTS: Transmission was compatible with an AR (n = 33) or autosomal dominant (AD, n = 26) inheritance, assuming that familial SSNS is a monogenic trait. Clinical features did not differ between AR and AD groups. All patients, including primary (n = 7) and secondary steroid resistant nephrotic syndrone (SRNS), (n = 13) were sensitive to additional immunosuppressive therapy. Both HLA-DQA1 variations were found to be highly linked to the disease (OR = 4.34 and OR = 4.89; p < 0.001). Exome sequencing did not reveal any pathogenic mutation, neither did EMP2 sequencing. CONCLUSIONS: Taken together, these results highlight the clinical and genetic heterogeneity in familial SSNS. Clinical findings sustain an immune origin in all patients, whatever the initial steroid-sensitivity. The absence of a variant shared by two families and the HLA-DQA1 variation enrichments suggest a complex mode of inheritance.


Subject(s)
Glucocorticoids/therapeutic use , HLA-DQ alpha-Chains/genetics , Membrane Glycoproteins/genetics , Nephrotic Syndrome/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Genetic Heterogeneity , Genetic Predisposition to Disease , Humans , Infant , Male , Middle Aged , Mutation , Nephrotic Syndrome/drug therapy , Sequence Analysis, DNA/methods , Young Adult
5.
Sultan Qaboos Univ Med J ; 15(2): e226-33, 2015 May.
Article in English | MEDLINE | ID: mdl-26052456

ABSTRACT

OBJECTIVES: This study aimed to describe the epidemiology of diabetes mellitus over the past two decades in Oman, particularly in terms of its prevalence and incidence. In addition, the study sought to estimate the future incidence of diabetes in Oman. METHODS: Three national and three regional surveys conducted between 1991 and 2010 were analysed to obtain the age-adjusted prevalence and undiagnosed proportion of type 2 diabetes mellitus (T2DM) among Omani subjects aged ≥20 years. Diabetes mellitus registers and published studies were used to determine incidence rates of both type 1 diabetes mellitus (T1DM) and T2DM in Oman. Linear regression was used to determine trends and projections for diabetes in 2050. RESULTS: The age-adjusted prevalence of T2DM in Oman varied from 10.4% to 21.1%, while the highest prevalence of impaired fasting glucose was found in males (35.1%). In comparison to men, higher incidence rates of T2DM were found in women (2.7 cases compared to 2.3 cases per 1,000 person-years, respectively). No significant trends were observed for the prevalence or incidence of T2DM in both genders. Undiagnosed T2DM was more common in men (range: 33-68%) than women (range: 27-53%). The results of this study show that by 2050, there will be an estimated 350,000 people with T2DM living in Oman (a 174% increase compared to estimates for 2015). CONCLUSION: Health authorities need to prioritise diabetes prevention and control in order to prevent or delay long-term complications and avert a potential epidemic of diabetes in Oman.

6.
Exp Clin Transplant ; 13 Suppl 1: 156-8, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25894146

ABSTRACT

OBJECTIVES: Nephropathy from BK virus (BKV) infection is a growing challenge in kidney transplant recipients globally. It is the result of contemporary potent immunosuppressives aimed at reducing acute rejection and improving allograft survival. Untreated BK virus infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening for early detection and prevention of symptomatic BK virus nephropathy may improve outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous immunoglobulin have been used. Since the introduction of the new immunosuppressive agents in the transplant regimen at the Royal Hospital, Few cases of BK virus have been detected, and the challenge was to decide upon the best treatment option. MATERIALS AND METHODS: The audit was carried out at the Royal Hospital-Oman between January 2010 and December 2012. The nephrology consultant and the clinical pharmacist reviewed all the BK cases and the Royal Hospital. Extensive literature review carried out by the pharmacist to look into the prevalence, prognosis and treatment of BK nephropathy. A treatment protocol was prepared by the clinical pharmacist through guidance of the consultant and was peer reviewed by team of clinical pharmacists and nephrology doctors and approved by the consultant. RESULTS: The audit included 19 patients with positive BK virus ployoma nephropathy. The treatment options were applied stepwise in all the patients with BK virus nephropathy with success rate more than 70%. CONCLUSIONS: BK virus nephropathy is emerging at an alarming rate and requires increasing awareness. The uses of current treatment options are still questionable. Our audit confirms that reducing immunosuppression appears to be the criterian standard for the treatment of BK nephropathy.


Subject(s)
Antiviral Agents/therapeutic use , BK Virus/pathogenicity , Hospitals , Immunosuppressive Agents/adverse effects , Kidney Transplantation/adverse effects , Opportunistic Infections/drug therapy , Polyomavirus Infections/drug therapy , Tumor Virus Infections/drug therapy , Adolescent , Adult , BK Virus/immunology , Child , Female , Humans , Immunocompromised Host , Male , Medical Audit , Middle Aged , Oman/epidemiology , Opportunistic Infections/diagnosis , Opportunistic Infections/epidemiology , Opportunistic Infections/immunology , Opportunistic Infections/virology , Patient Care Team , Polyomavirus Infections/diagnosis , Polyomavirus Infections/epidemiology , Polyomavirus Infections/immunology , Polyomavirus Infections/virology , Prevalence , Risk Factors , Time Factors , Treatment Outcome , Tumor Virus Infections/diagnosis , Tumor Virus Infections/epidemiology , Tumor Virus Infections/immunology , Tumor Virus Infections/virology , Young Adult
7.
High Blood Press Cardiovasc Prev ; 22(1): 83-97, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25404558

ABSTRACT

Hypertension (HTN) is a major independent risk factor for the development of stroke, coronary artery disease (CAD), peripheral arterial disease (PAD), heart failure (HF) and chronic kidney disease (CKD). HTN is a growing public health problem in Oman, almost certainly the most prevalent modifiable risk factor for cardiovascular disease (CVD). The risk of CVD in patients with HTN can be greatly reduced with lifestyle modifications and effective antihypertensive therapy. Randomized trials have shown that blood pressure (BP) lowering produces rapid reductions in CV risk. Several studies have shown that the majority of the hypertensive patients remain uncontrolled. It is well established that the observed poor control of the disease is not only related to poor adherence to medications, but also to limited awareness and adherence to evidence-based management of hypertension among physicians. Several guidelines for the management of patients with hypertension have been published. However, the aim of this document is to provide the busy physicians in Oman with more concise and direct approach towards implementing these guidelines into clinical practice.


Subject(s)
Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Cardiology/standards , Hypertension/drug therapy , Practice Patterns, Physicians'/standards , Blood Pressure Determination/standards , Humans , Hypertension/diagnosis , Hypertension/epidemiology , Hypertension/physiopathology , Oman/epidemiology , Predictive Value of Tests , Risk Factors , Risk Reduction Behavior , Treatment Outcome
8.
Hum Mutat ; 35(2): 178-86, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24227627

ABSTRACT

Mutations in the NPHS2 gene encoding podocin are implicated in an autosomal-recessive form of nonsyndromic steroid-resistant nephrotic syndrome in both pediatric and adult patients. Patients with homozygous or compound heterozygous mutations commonly present with steroid-resistant nephrotic syndrome before the age of 6 years and rapidly progress to end-stage kidney disease with a very low prevalence of recurrence after renal transplantation. Here, we reviewed all the NPHS2 mutations published between October 1999 and September 2013, and also all novel mutations identified in our personal cohort and in international genetic laboratories. We identified 25 novel pathogenic mutations in addition to the 101 already described. The mutations are distributed along the entire coding region and lead to all kinds of alterations including 53 missense, 17 nonsense, 11 small insertions, 26 small deletions, 16 splicing, two indel mutations, and one mutation in the stop codon. In addition, 43 variants were classified as variants of unknown significance, as these missense changes were exclusively described in the heterozygous state and/or considered benign by prediction software. Genotype-phenotype analyses established correlations between specific variants and age at onset, ethnicity, or clinical evolution. We created a Web database using the Leiden Open Variation Database (www.lovd.nl/NPHS2) software that will allow the inclusion of future reports.


Subject(s)
Intracellular Signaling Peptides and Proteins/genetics , Membrane Proteins/genetics , Mutation , Nephrotic Syndrome/congenital , Adult , Age of Onset , Animals , Child, Preschool , Disease Models, Animal , Genetic Variation , Genotype , Humans , Intracellular Signaling Peptides and Proteins/metabolism , Membrane Proteins/metabolism , Nephrotic Syndrome/genetics , Nephrotic Syndrome/pathology , Phenotype , Polymorphism, Single Nucleotide , Software
9.
J Am Soc Nephrol ; 22(2): 239-45, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21258034

ABSTRACT

The recent identification of mutations in the INF2 gene, which encodes a member of the formin family of actin-regulating proteins, in cases of familial FSGS supports the importance of an intact actin cytoskeleton in podocyte function. To determine better the prevalence of INF2 mutations in autosomal dominant FSGS, we screened 54 families (78 patients) and detected mutations in 17% of them. All mutations were missense variants localized to the N-terminal diaphanous inhibitory domain of the protein, a region that interacts with the C-terminal diaphanous autoregulatory domain, thereby competing for actin monomer binding and inhibiting depolymerization. Six of the seven distinct altered residues localized to an INF2 region that corresponded to a subdomain of the mDia1 diaphanous inhibitory domain reported to co-immunoprecipitate with IQ motif-containing GTPase-activating protein 1 (IQGAP1). In addition, we evaluated 84 sporadic cases but detected a mutation in only one patient. In conclusion, mutations in INF2 are a major cause of autosomal dominant FSGS. Because IQGAP1 interacts with crucial podocyte proteins such as nephrin and PLCε1, the identification of mutations that may alter the putative INF2-IQGAP1 interaction provides additional insight into the pathophysiologic mechanisms linking formin proteins to podocyte dysfunction and FSGS.


Subject(s)
Glomerulosclerosis, Focal Segmental/genetics , Microfilament Proteins/genetics , Mutation , Actinin/genetics , Adolescent , Adult , Aged , Amino Acid Sequence , Child , Child, Preschool , Formins , Glomerulosclerosis, Focal Segmental/etiology , Humans , Infant , Microfilament Proteins/physiology , Middle Aged , Molecular Sequence Data , ras GTPase-Activating Proteins/physiology
10.
Exp Clin Transplant ; 8(4): 303-6, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21143096

ABSTRACT

OBJECTIVES: Renal transplant, especially from genetically related living-donors, is associated with excellent results. The security and free will of the donor are of paramount importance. A significant percentage of such transplants are not accomplished for both medical and nonmedical reasons. MATERIALS AND METHODS: We looked retrospectively into the causes of nonaccomplishment of renal transplants from living-related donor transplants at our center from January 2006 through June 2008. RESULTS: During this period, 69 and 99 potential renal transplant recipient and donors were investigated. Transplants could be performed only in 35 patients (51%). About 59% of the donors were rejected or declined. Reasons for exclusion were immunologic in 14 donors (14%). Medical and nonmedical conditions precluded donation in 35 donors (35%) and 12 donors (12%). Medical reasons consisted mainly of undiagnosed hypertension, obesity, diabetes mellitus, and renal anomalies. In the recipients, the major reason was option for transplant tourism, occurred in 11 cases (16%). CONCLUSIONS: A substantial number of investigated recipients and donors for living-related transplant are not accomplished. The major reasons are medical for the donor and transplant tourism for the recipient.


Subject(s)
Arabs/statistics & numerical data , Donor Selection/statistics & numerical data , Kidney Transplantation/ethnology , Living Donors/supply & distribution , Medical Tourism/statistics & numerical data , Adult , Female , Humans , Male , Middle Aged , Oman , Retrospective Studies
11.
Oman Med J ; 25(4): e013, 2010 Oct.
Article in English | MEDLINE | ID: mdl-28845216

ABSTRACT

Hypercalcemia may follow hypocalcemia in the course of acute renal failure (also named now as acute kidney injury) secondary to rhabdomyolysis. The clinician should be aware of this calcium kinetics to avoid the complications of both hypocalcemia and hypercalcemia that may occur at few days interval during the recovery phase. We present herewith the case of a young gentleman who developed anuric ARF due to a strenuous exercise induced rhabdomyolysis. He was treated with supportive, corrective and dialysis measures. The progress was favourable with a diuretic phase. During the diuretic phase, he developed progressive hypercalcemia that reached up to 3.54 mEq/lwith constipation and drowsiness. Investigations showed besides stigmata of rhabdomyolysis and ARF, low initial levels of vitamin D metabolites. The calcemia eventually normalized with fluids, dialysis and a single dose of Pamidronate Sodium . The patient was discharged 3 weeks after admission with a recovered clinical condition, improved renal functions and normal calcemia. The biphasic kinetics of calcium in this setting is ocumented. We conclude that serum corrected calcium should be monitored in the context of ARF due to rhabdomyolysis.

12.
Exp Clin Transplant ; 7(1): 62-5, 2009 Mar.
Article in English | MEDLINE | ID: mdl-19364316

ABSTRACT

OBJECTIVES: Acute purulent pericarditis is a lifethreatening disease, although it is becoming uncommon in the era of antibiotics. MATERIALS AND METHODS: We present a case of fatal acute massive purulent pericarditis in a kidney transplant recipient. RESULTS: A 46-year-old woman had an unrelated commercial renal transplant in 2003. She had a history of diabetes mellitus and hepatitis C infection. Kaposi sarcoma developed in the posttransplant period. Her last admission was prompted by the development of acute rejection confirmed by transplant biopsy, and she was treated with intravenous methylprednisolone. Three days before her death, thrombophlebitis of the right forearm was noted. We postulate that this could have been the source of the fulminant purulent pericarditis, as the organism in the pericardial fluid was Staphylococcus aureus, a common pathogen in thrombophlebitis. She was initially resuscitated after cardiac arrest but died shortly after. CONCLUSIONS: Severe purulent pericarditis in the immunocompromised patient can occur abruptly. The source of infection may show minimal signs and symptoms. Thrombophlebitis and other apparently minor infections should not be overlooked in such patients.


Subject(s)
Catheter-Related Infections/microbiology , Kidney Transplantation/adverse effects , Pericardial Effusion/microbiology , Pericarditis/microbiology , Staphylococcus aureus/isolation & purification , Thrombophlebitis/microbiology , Acute Disease , Anti-Bacterial Agents/therapeutic use , Catheter-Related Infections/complications , Catheter-Related Infections/diagnostic imaging , Catheter-Related Infections/therapy , Fatal Outcome , Female , Graft Rejection/etiology , Graft Rejection/therapy , Heart Arrest/microbiology , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Methylprednisolone/administration & dosage , Middle Aged , Pericardial Effusion/diagnostic imaging , Pericardial Effusion/therapy , Pericardiectomy , Pericarditis/diagnostic imaging , Pericarditis/therapy , Radiography , Renal Dialysis , Resuscitation , Thrombophlebitis/complications , Thrombophlebitis/diagnostic imaging , Thrombophlebitis/therapy , Treatment Outcome
13.
Oman Med J ; 23(2): 101-3, 2008 Apr.
Article in English | MEDLINE | ID: mdl-22379546

ABSTRACT

The spectrum of tropical nephropathies includes Acute Renal Failure (ARF) or Acute Kidney Injury (AKI) due to infective agents that are endemic in the tropics which include Leptospira (LS) and Dengue Viruses (DV). The major histological feature is Acute Tubular Necrosis (ATN).(1, 2)We report the case of a patient who presented ARF with co-infection with both agents. The clinical manifestations were consistent with both diseases. A renal treatment was supportive and the outcome was positive.We conclude that co-infection with these two tropical agents was possible. It may have been overlooked when the diagnosis of one agent was confirmed, especially that aware of the possibility of co-infection, as the management may be different. Spontaneous full recovery in these circumstances is still possible with supportive treatment.

14.
Exp Clin Transplant ; 2(2): 217-20, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15859931

ABSTRACT

During the seventies, sporadic renal transplants were performed in few MESOT-region countries, mainly Turkey, Iran, Egypt, and Lebanon. Since the introduction of cyclosporine in the early eighties, transplantation has become the preferred therapeutic modality for end-stage renal failure. In 1986, the Islamic theologians (Al Aloma) issued what became known as the Amman declaration, in which they accepted brain death and retrieval and transplantation of organs from living and cadaveric donors. Based on this and similar declarations, all Middle Eastern countries except Egypt passed laws that allow cadaveric transplantation and regulate live donations. Iran, Turkey, Saudi Arabia, Kuwait, Tunisia, Jordan, and Lebanon all have current active cadaveric programs and perform liver, heart, pancreas, and lung transplants. More than 5088 renal transplants/year are performed in the region with Iran leading with 1600. The cumulative number of renal transplant patients is now nearly 60,000. With a 2003 population of 600,682,175, the rate/million for renal transplantation in the MESOT region is a mere 9/million. Rates of renal transplantation range from 31/million in some countries to 0 in others. The major obstacle in establishing an accurate number of transplants is "tourist transplantation," in which the same transplanted patients are registered in different countries. Although cadaveric programs have been active for more than 10 years, live-related and nonrelated transplants account for nearly 85% of the total transplants. The data presented were collected from MESOT representatives in the region and from publications. For proper compilation of the registry, a format is being proposed that will be presented at the Congress for review and adaptation. Even with the limited resources in the region, immunosuppressive drugs for induction and maintenance therapy are available and are used. Costs for transplantation and immunosuppressive therapy are either totally or heavily supported by governmental agencies.


Subject(s)
Organ Transplantation , Registries , Societies, Medical , Humans , Kidney Transplantation/statistics & numerical data , Living Donors/statistics & numerical data , Middle East , Organ Transplantation/statistics & numerical data
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